Cyclophosphamide, Adriamycin, vincristine, and dexamethasone in the treatment of bulky central nervous system lymphoma

Russell, Neville; Dennery, Jean; Richard, Marie-Claude; Atack, E A; Eapen, Libni; Girard, A.; Maroun, J.; Grahovac, Zvonimir; Bélanger, Garry

doi:10.1007/978-1-4613-2297-9_59

Cited by 11 publications

(9 citation statements)

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“…Chemotherapy has become an important component of treatment for cerebral lymphoma, and it is evident that drugs must penetrate a normal BBB to adequately treat all regions of tumor. Many combination regimens designed for systemic lymphomas have been adopted for use in PCNSL; however, most use agents that do not penetrate the BBB [9][10][11][12]. Although these regimens may produce short-lived responses, recurrence is often seen in regions remote from the original site of disease, likely from tumor behind a normal BBB which was not adequately treated {lo, 12, 131.…”

Section: Discussionmentioning

confidence: 99%

Cerebral lymphoma presenting as a nonenhancing lesion on computed tomographic/ magnetic resonance scan

DeAngelis

1993

Annals of Neurology

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Cerebral lymphoma is usually identified on computed tomographiclmagnetic resonance scan as a homogeneously contrast-enhancing periventricular mass lesion. We present 10 patients with cerebral lymphoma who had nonenhancing tumor on computed tomographic (2 patients) or magnetic resonance scan (8 patients) either at the time of diagnosis or recurrence. The absence of enhancement caused diagnostic delay in all patients and suggests that tumor resides behind an intact bloodbrain barrier, raising important therapeutic implications in the design of chemotherapeutic regimens. Cancer Center between July 1985 and October 1991. Eight (10%) had nonenhancing PCNSL lesions; 2 additional patients with metastatic cerebral lymphoma also had nonenhancing tumors. All patients had pathological confirmation of cerebral lymphoma, and tumor was correlated with scan abnormalities at autopsy in 6 patients. In the remaining 4, all of whom had at least one enhancing lesion at presentation, PCNSL was established by biopsy. The nature of coexisting or subsequent nonenhancing lesions was inferred from the patient's clinical course and follow-up of the radiographic abnormalities. All 10 patients were evaluated by MR scan; 8 had MRI studies with gadolinium, and 2 had contrast-enhanced CT scans. Nonenhancing lesions were abnormalities apparent on T2-weighted MR images that were not evident on TI images after gadolinium administration or on contrast CT scan. All nonenhancing lesions were > 1 cm, and 9 of 10 patients had confluent lesions that were multiple or involved large regions of brain. Small nonenhancing white matter abnormalities often attributed to small vessel disease were not included in our definition of nonenhancing lesions and were not similar to the abnormalities noted in these patients [63. At the time scans were obtained, only 4 patients were taking corticosteroids; 6 were not. ResultsSix patients were men and 4 were women; the mean age was 53 years (range, 37-80 yr). All the patients were human immunodeficiency virus type 1 negative; 2 patients developed systemic lymphoma with parenchymal brain involvement after a T-cell-depleted allogeneic bone marrow transplant for chronic myelogenous leukemia (Table).Nonenhancing lesions were seen as the only radiographic abnormality in 5 patients (Fig 1). The remaining 5 had at least one enhancing lesion identified on the same scan; however, 2 of these patients had only tiny punctate areas of enhancement in the setting of large nonenhancing abnormalities. Nonenhancing lesions were seen at the time of diagnosis in 4 patients and at recurrence in 6.In 6 patients, the lesions had mass effect in the absence of enhancement, suggesting a space-occupying process (Fig 2). However, 4 patients had T2 abnormalities not associated with mass effect, that proved to represent tumor on postmortem examination. Furthermore, tumor could be identified in radiographically normal regions, even on T2-weighted MR images, in all 6 autopsied patients. The final MR scan in these patients was taken an average of 40 days...

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Section: Discussionmentioning

confidence: 99%

Cerebral lymphoma presenting as a nonenhancing lesion on computed tomographic/ magnetic resonance scan

DeAngelis

1993

Annals of Neurology

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“…Despite the shortcomings of this study, it is clear that MCHOD has activity in PCNSL, though the lack of response in four patients and the short response duration in some others suggests incomplete therapy of intraparenchymal tumor foci. We believe that MTX provided much of the anti-neoplastic activity, with CHOD only contributing to the responses seen in larger mass lesions [17,[19][20][21]. MCHOD does not appear to be superior to HDMTX monotherapy, achieving lesser or similar response durations with greater toxicity.…”

Section: Discussionmentioning

confidence: 99%

“…CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) is thought to be the best available initial therapy for NHL [16]. In an attempt to improve upon the results of therapy with a single agent and decrease the possibility of drug resistance, we administered 'CHOD' [17] (substituting dexamethasone for prednisone in CHOP) with HDMTX ('MCHOD').…”

Section: Introductionmentioning

confidence: 99%

Therapy of primary central nervous system lymphoma with pre-irradiation methotrexate, cyclophosphamide, doxorubicin, vincristine, and dexamethasone (MCHOD)

et al. 1996

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Prior studies have suggested that pre-irradiation methotrexate (MTX)-based chemotherapy improves duration of response and survival in primary central nervous system lymphoma (PCNSL). To circumvent the potential emergence of drug resistance, we combined high-dose MTX with agents highly active against systemic lymphoma. Patients received three week cycles of CHOD (cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, and vincristine 1.4 mg/m2 [2 mg maximum] on day 1; dexamethasone 10 mg/m2 days 1-5), and MTX (3.5 gm/m2) with leucovorin rescue on day 8 (or on recovery from the CHOD nadir). Whole brain irradiation (WBRT) was planned after at least three cycles. Eighteen patients were treated. Complete responses were seen in eleven patients, and partial responses in three. Four progressed during therapy, three succumbing to progressive disease and one subsequently responding to WBRT. Response duration was 37.5 months in those responding to therapy. The time to progression for all eighteen patients was 19.5 months. Medial survival was 25.5 months. Disease-free survival was 50% at 38 months in MCHOD responders. Grade 3 or 4 myelotoxicity was seen in 19 of 50 cycles. There were three instances of neutropenic fever, three of azotemia, two of deep vein thrombosis, and one each of community-acquired pneumonia, intracranial hemorrhage, superior vena cava syndrome, and hepatotoxicity. Late radiation-related toxicities were seen in two patients. Pre-irradiation MCHOD has activity against PCNSL, but appears to be no better than MTX monotherapy and has greater toxicity.

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“…In addition, with the occasional exception of highdose intravenous meth~trexate,~~ chemotherapeutic agents have not resulted in the increased therapeutic efficacy seen in lymphoma arising elsewhere in the body. 18,20322,26- 28 The current report describes three new approaches in the diagnosis and treatment of these tumors. 6.…”

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confidence: 99%

Developments in the diagnosis and treatment of primary CNS lymphoma: A prospective series

Neuwelt

Frenkel

Gumerlock

et al. 1986

Cancer

116

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Current experience with 12 patients studied prospectively suggests a new approach in the diagnosis and treatment of primary central nervous system (CNS) lymphoma, integrating the techniques of needle brain biopsy, immunohistochemical staining for monoclonal antibody and chemotherapeutic drug delivery in association with blood-brain barrier modification. Computed tomography (CT)-guided needle biopsy of deep parenchymal lesions contributed to the diagnosis in six patients. Immunohistochemical staining methods detected monoclonal immunoglobulins in those patients so tested. Following diagnosis, the patients have been treated with multi-agent chemotherapy in conjunction with osmotic blood-brain barrier modification (five without antecedent cranial irradiation) with an initial complete response rate by CT scan in nine patients, a median follow-up of 19 months from diagnosis, and a 1-year survival of 75%. This experience emphasizes the value of CT-guided stereotaxic or CT-guided needle biopsy, which limits the need for therapy without a diagnosis or the need for a major craniotomy in what are commonly deep, paraventricular lesions. Immunoperoxidase cytochemical stains can detect monoclonal immunoglobulin characteristic of CNS B-cell malignant lymphomas and provide an important diagnostic aid when only modest quantities of tissue or cells are obtained. Finally, chemotherapy administered in conjunction with osmotic blood-brain barrier modification results in a clinical response rate and survival that are at least as effective as radiotherapy as a primary therapeutic modality.

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Cyclophosphamide, Adriamycin, vincristine, and dexamethasone in the treatment of bulky central nervous system lymphoma

Cited by 11 publications

References 11 publications

Cerebral lymphoma presenting as a nonenhancing lesion on computed tomographic/ magnetic resonance scan

Cerebral lymphoma presenting as a nonenhancing lesion on computed tomographic/ magnetic resonance scan

Therapy of primary central nervous system lymphoma with pre-irradiation methotrexate, cyclophosphamide, doxorubicin, vincristine, and dexamethasone (MCHOD)

Developments in the diagnosis and treatment of primary CNS lymphoma: A prospective series

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